Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study

The COVID-19 pandemic has urged for the repurposing of existing drugs for rapid management and treatment. Renin inhibitors down regulation of ACE2, which is an essential receptor for SARS-CoV-2 infection that is responsible for COVID-19, in addition to their ability to act as protease inhibitors were encouraging aspects for their investigation as possible inhibitors of main protease of SARS-CoV-2 via computational studies. A Pharmacophore model was generated using the newly released SARS-COV-2 main protease inhibitors. Virtual screening was performed on renin inhibitors, and Drug likeness filter identified remikiren and OIU as hits. Molecular docking for both compounds showed that the orally active renin inhibitor remikiren (Ro 42-5892) of Hoffmann-La Roche exhibited good molecular interaction with Cys145 and His41 in the catalytic site of SARS-CoV-2 main protease. Molecular dynamics simulation suggested that the drug is stable in the active site of the enzyme.

Automated summary

The COVID-19 pandemic has led to the repurposing of existing drugs, with renin inhibitors showing potential as inhibitors of the main protease of SARS-CoV-2. Virtual screening and molecular docking indicated that remikiren could interact well with the catalytic site of the main protease, suggesting its stability as a potential treatment option.